Molecular Regulatory Pathways Link Sepsis With Metabolic Syndrome: Non-coding RNA Elements Underlying the Sepsis/Metabolic Cross-Talk

Abstract

Sepsis and metabolic syndrome (MetS) are both inflammation-related entities with high impact for human health and the consequences of concussions. Both represent imbalanced parasympathetic/cholinergic response to insulting triggers and variably uncontrolled inflammation that indicates shared upstream regulators, including short microRNAs (miRs) and long non-coding RNAs (lncRNAs). These may cross talk across multiple systems, leading to complex molecular and clinical outcomes. Notably, biomedical and RNA-sequencing based analyses both highlight new links between the acquired and inherited pathogenic, cardiac and inflammatory traits of sepsis/MetS. Those include the HOTAIR and MIAT lncRNAs and their targets, such as miR-122, −150, −155, −182, −197, −375, −608 and HLA-DRA. Implicating non-coding RNA regulators in sepsis and MetS may delineate novel high-value biomarkers and targets for intervention.

The Neat Dance of COVID-19: NEAT1, DANCR, and Co-Modulated Cholinergic RNAs Link to Inflammation

“…The lncRNA-mediated “overwatch” may avert cytokine storms characteristic of sepsis; and prevent detrimental life-threatening states which may develop where these and other mediators fail to harness overwhelming inflammation ( 35 ). Correspondingly, changes in inflammation-related ncRNAs, coupled with modified cholinergic surveillance, are evident in infectious, neuro-inflammatory and other conditions, including brain ramifications ( 30 , 37 , 119 , 128 – 130 ).…”

“…Under acute or chronic challenges, ncRNAs interact with other ncRNAs, coding messenger RNAs (mRNAs), or directly with proteins, modifying their actions and affecting various clinical conditions including inflammation ( 32 , 33 ). Specifically, several ncRNAs react to chronic, subacute inflammation, such as in the metabolic syndrome and its components and in the organismal response to infections ( 34 , 35 ). Therefore, impaired ncRNA reactions in clinical scenarios may include inflammation-induced “collateral damage”.…”

Elevated liver fibrosis index FIB-4 is associated with poor clinical outcomes in patients with sepsis, an observational cohort study

“…Notably, recent research found that NAFLD predisposing genes were also involved in the pathogenesis of phenotypes of sepsis [12]. Moreover, biomedical and RNA-sequencing based analyses both highlighted signi cant connections between the acquired and inherited pathogenic, cardiac and in ammatory traits of sepsis and MetS [13]. Then, we also noted that both advanced cirrhosis and MetS lead to poor prognosis of sepsis [14,15].…”

Population‐based data registries suggest novel insight into malignancy and metabolism

“…11 It may be plausible to suspect that noncoding RNA and associated inflammation underlie part of the association observed by Levi and colleagues in their current study. 12,14 Furthermore, in the context of the current study by Levi et al, large-scale data registries may facilitate the identification of such associations, aiming at large operational scale and freedom from bias. 11 Such a hypothesis requires further investigation of involved mechanisms, with noncoding RNA regulators as a stepping stone for delineating putative links between malignancy and MetS.…”

“…In the context of MetS, anxiety and reaction to infection, there is evidence implicating noncoding RNA mediators as dovetails connecting seemingly distinct clinical entities, with inflammation and neural machinery as key underpinnings for these links. 12,14 Furthermore, in the context of the current study by Levi et al, large-scale data registries may facilitate the identification of such associations, aiming at large operational scale and freedom from bias. Because this is not feasible in many instances, interconnectivity between several databases may hold promise.…”